Schizophrenia is a prevalent mental health disorder that creates enormous social, economic, and interpersonal hardships for patients and their families. Although hallucinations and delusions are the most salient symptoms of this disease, schizophrenia also involves pervasive cognitive deficits that are key predictors of long-term outcome and are not substantially ameliorated by current medications. Progress in treating these symptoms requires basic science research on the neural and cognitive systems that are dysfunctional in schizophrenia (for the development of targeted treatments) and highly precise measures of these systems (for the assessment of new treatments). The purpose of the present proposal is to advance our understanding of a set of important basic science issues and simultaneously lay the groundwork for the next steps in clinical research. Specifically, the proposed project will explore the mechanisms by which working memory representations control the operation of attention. Current research indicates that this is a key area of dysfunction in schizophrenia, but insufficient basic science is available to guide the next steps of clinical research in this area. In addition, this is a key area of research for understanding the overall architecture of the human mind. The proposed research will explore the processes and circuits by which working memory representations exert control over attention, focusing on the visual modality because of our rich knowledge base about the anatomy, physiology, and function of the visual system. We will use a combination of eye tracking, event-related potentials (ERPs), and psychophysics so that we can precisely determine whether attention is covertly and overtly directed toward items that either match or mismatch items being held in working memory. We will assess both the cognitive processes involved in using working memory to guide attention and the neural circuits that mediate between working memory representations and the implementation of selective attention. This research will feed directly into our program of translational research on cognitive dysfunction in schizophrenia and our efforts to develop next-generation measures that can be used in the development and assessment of new treatments for this disease. PUBLIC HEALTH RELEVANCE: Schizophrenia is a major mental health disorder, and cognitive dysfunction is a key target for future treatments of this disease. Recent research shows that deficits in the ability to use working memory to control attention are a major component of the cognitive dysfunction profile in schizophrenia, but relatively little basic science on this topic is available to guide the next steps of clinical research. The present project aims to provide a clearer understanding of the cognitive and neural mechanisms by which working memory controls attention in the healthy brain, which will provide the basic science backbone for future research designed to understand and treat cognitive dysfunction in schizophrenia.